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Tissue-Specific Stem Cells
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Activated Spinal Cord Ependymal Stem Cells Rescue Neurological Function†‡§
Article first published online: 28 JAN 2009
DOI: 10.1002/stem.24
Copyright © 2009 AlphaMed Press
Additional Information
How to Cite
Moreno-Manzano, V., Rodríguez-Jiménez, F. J., García-Roselló, M., Laínez, S., Erceg, S., Calvo, M. T., Ronaghi, M., Lloret, M., Planells-Cases, R., Sánchez-Puelles, J. M. and Stojkovic, M. (2009), Activated Spinal Cord Ependymal Stem Cells Rescue Neurological Function. STEM CELLS, 27: 733–743. doi: 10.1002/stem.24
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Author contributions: V.M.-M., F.J.R.-J., and M.S.: conceived and designed the experiments; V.M.-M., F.J.R.-J., M.G.-R., S.L., S.E., M.T.C., M.R., and M.L.: performed the experiments; V.M.-M., F.J.R.-J., R.P.-C., J.M.S.-P., and M.S.: analyzed the data; V.M.-M., F.J.R.-J., R.P.-C., J.M.S.-P., and M.S.: wrote the article.
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Disclosure of potential conflicts of interest is found at the end of this article.
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First published online in STEM CELLSExpress January 28, 2009.
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Publication History
- Issue published online: 2 MAR 2009
- Article first published online: 28 JAN 2009
- Accepted manuscript online: 28 JAN 2009 12:00AM EST
- Manuscript Accepted: 27 DEC 2008
- Manuscript Received: 28 OCT 2008
Funded by
- Confocal Microscopy service of the Centro de Investigacion Príncipe Felipe
- Spanish Program of Regenerative Medicine Conselleria de Sanidad de la Generalidad Valenciana-Instituto de Salud Carlos III
- Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III. Grant Number: RD06/0010/1006
- Ministerio de Educación. Grant Number: SAF2007-63714
- Ciencia y Tecnología. Grant Number: SAF2007-63193
Keywords:
- Ependymal cell;
- Spinal cord injury repair;
- Stem/progenitors cell;
- Oligodendrocyte;
- Motoneurons
Abstract
Spinal cord injury (SCI) is a major cause of paralysis. Currently, there are no effective therapies to reverse this disabling condition. The presence of ependymal stem/progenitor cells (epSPCs) in the adult spinal cord suggests that endogenous stem cell-associated mechanisms might be exploited to repair spinal cord lesions. epSPC cells that proliferate after SCI are recruited by the injured zone, and can be modulated by innate and adaptive immune responses. Here we demonstrate that when epSPCs are cultured from rats with a SCI (ependymal stem/progenitor cells injury [epSPCi]), these cells proliferate 10 times faster in vitro than epSPC derived from control animals and display enhanced self renewal. Genetic profile analysis revealed an important influence of inflammation on signaling pathways in epSPCi after injury, including the upregulation of Jak/Stat and mitogen activated protein kinase pathways. Although neurospheres derived from either epSPCs or epSPCi differentiated efficiently to oligodendrocites and functional spinal motoneurons, a better yield of differentiated cells was consistently obtained from epSPCi cultures. Acute transplantation of undifferentiated epSPCi or the resulting oligodendrocyte precursor cells into a rat model of severe spinal cord contusion produced a significant recovery of motor activity 1 week after injury. These transplanted cells migrated long distances from the rostral and caudal regions of the transplant to the neurofilament-labeled axons in and around the lesion zone. Our findings demonstrate that modulation of endogenous epSPCs represents a viable cell-based strategy for restoring neuronal dysfunction in patients with spinal cord damage. STEM CELLS2009;27:733–743